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Protein

Bis(5'-adenosyl)-triphosphatase

Gene

Fhit

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Cleaves P1-P3-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P1-P4-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P1-P3-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity (By similarity). Functions as tumor suppressor.By similarity2 Publications

Catalytic activityi

P1-P3-bis(5'-adenosyl) triphosphate + H2O = ADP + AMP.

Cofactori

Mg2+By similarity, Mn2+By similarity, Ca2+By similarity, Co2+By similarityNote: Divalent metal cations. Mg2+, but Mn2+ and to a lesser extent Ca2+ or Co2+ can be substituted; but not Zn2+, Cd2+ or Ni2+.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei8SubstrateBy similarity1
Binding sitei27SubstrateBy similarity1
Binding sitei83SubstrateBy similarity1
Active sitei96Tele-AMP-histidine intermediateBy similarity1
Binding sitei98SubstrateBy similarity1
Sitei114Important for induction of apoptosisBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi89 – 92SubstrateBy similarity4

GO - Molecular functioni

  • bis(5'-adenosyl)-triphosphatase activity Source: UniProtKB
  • catalytic activity Source: ProtInc
  • hydrolase activity Source: UniProtKB
  • identical protein binding Source: MGI
  • nickel cation binding Source: MGI
  • nucleotide binding Source: UniProtKB-KW
  • ubiquitin protein ligase binding Source: MGI

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Transcription, Transcription regulation
LigandMagnesium, Manganese, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Bis(5'-adenosyl)-triphosphatase (EC:3.6.1.29)
Alternative name(s):
AP3A hydrolase
Short name:
AP3Aase
Diadenosine 5',5'''-P1,P3-triphosphate hydrolase
Dinucleosidetriphosphatase
Fragile histidine triad protein
Gene namesi
Name:Fhit
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1277947 Fhit

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

No visible phenotype at birth, but about 30% of the mice lacking one or both copies of Fhit died for unknown reasons at an age of about 19 months. This might be due to increased susceptibility to infections. Mice lacking one or both copies of Fhit show increased susceptibility to carcinogens.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001097901 – 150Bis(5'-adenosyl)-triphosphataseAdd BLAST150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei114Phosphotyrosine; by SRCBy similarity1
Modified residuei147PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylation at Tyr-114 by SRC is required for induction of apoptosis.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO89106
PaxDbiO89106
PRIDEiO89106

PTM databases

iPTMnetiO89106
PhosphoSitePlusiO89106
SwissPalmiO89106

Expressioni

Tissue specificityi

Expressed in heart, brain, lung and skeletal muscle. Particularly strong expression in liver, testis and kidney, where it is confined to the tubular epithelium.2 Publications

Gene expression databases

BgeeiENSMUSG00000060579 Expressed in 183 organ(s), highest expression level in membranous labyrinth
CleanExiMM_FHIT
ExpressionAtlasiO89106 baseline and differential
GenevisibleiO89106 MM

Interactioni

Subunit structurei

Homodimer. Interacts with UBE2I. Interacts with MDM2. Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000123874

Structurei

3D structure databases

ProteinModelPortaliO89106
SMRiO89106
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 109HITPROSITE-ProRule annotationAdd BLAST108

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi94 – 98Histidine triad motif5

Phylogenomic databases

eggNOGiKOG3379 Eukaryota
COG0537 LUCA
GeneTreeiENSGT00510000047967
HOGENOMiHOG000164170
HOVERGENiHBG051614
InParanoidiO89106
KOiK01522
PhylomeDBiO89106

Family and domain databases

CDDicd01275 FHIT, 1 hit
Gene3Di3.30.428.10, 1 hit
InterProiView protein in InterPro
IPR039383 FHIT
IPR019808 Histidine_triad_CS
IPR001310 Histidine_triad_HIT
IPR011146 HIT-like
IPR036265 HIT-like_sf
PANTHERiPTHR23089 PTHR23089, 1 hit
PfamiView protein in Pfam
PF01230 HIT, 1 hit
SUPFAMiSSF54197 SSF54197, 1 hit
PROSITEiView protein in PROSITE
PS00892 HIT_1, 1 hit
PS51084 HIT_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

O89106-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFRDL
60 70 80 90 100
HPDEVADLFQ VTQRVGTVVE KHFQGTSITF SMQDGPEAGQ TVKHVHVHVL
110 120 130 140 150
PRKAGDFPRN DNIYDELQKH DREEEDSPAF WRSEKEMAAE AEALRVYFQA
Length:150
Mass (Da):17,235
Last modified:January 23, 2007 - v3
Checksum:i27CBC57C5A4A0E2B
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PZ91E9PZ91_MOUSE
Bis(5'-adenosyl)-triphosphatase
Fhit
213Annotation score:
E9Q3M6E9Q3M6_MOUSE
Bis(5'-adenosyl)-triphosphatase
Fhit
57Annotation score:
E9PVU9E9PVU9_MOUSE
Bis(5'-adenosyl)-triphosphatase
Fhit
124Annotation score:
F6SV10F6SV10_MOUSE
Bis(5'-adenosyl)-triphosphatase
Fhit
100Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti135K → E in AAH12662 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AH006186 Genomic DNA Translation: AAC23967.1
AF047699 mRNA Translation: AAC24566.1
AF055573 mRNA Translation: AAC24117.1
BC012662 mRNA Translation: AAH12662.1
AH013372 Genomic DNA Translation: AAR17701.1
CCDSiCCDS49400.1
RefSeqiNP_001295215.1, NM_001308286.1
NP_034340.1, NM_010210.3
XP_006517990.1, XM_006517927.3
XP_011243034.1, XM_011244732.2
XP_017171336.1, XM_017315847.1
UniGeneiMm.397619
Mm.441926

Genome annotation databases

EnsembliENSMUST00000161302; ENSMUSP00000123874; ENSMUSG00000060579
ENSMUST00000162278; ENSMUSP00000124073; ENSMUSG00000060579
ENSMUST00000179394; ENSMUSP00000136011; ENSMUSG00000060579
GeneIDi14198
KEGGimmu:14198
UCSCiuc007sfj.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AH006186 Genomic DNA Translation: AAC23967.1
AF047699 mRNA Translation: AAC24566.1
AF055573 mRNA Translation: AAC24117.1
BC012662 mRNA Translation: AAH12662.1
AH013372 Genomic DNA Translation: AAR17701.1
CCDSiCCDS49400.1
RefSeqiNP_001295215.1, NM_001308286.1
NP_034340.1, NM_010210.3
XP_006517990.1, XM_006517927.3
XP_011243034.1, XM_011244732.2
XP_017171336.1, XM_017315847.1
UniGeneiMm.397619
Mm.441926

3D structure databases

ProteinModelPortaliO89106
SMRiO89106
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000123874

PTM databases

iPTMnetiO89106
PhosphoSitePlusiO89106
SwissPalmiO89106

Proteomic databases

MaxQBiO89106
PaxDbiO89106
PRIDEiO89106

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000161302; ENSMUSP00000123874; ENSMUSG00000060579
ENSMUST00000162278; ENSMUSP00000124073; ENSMUSG00000060579
ENSMUST00000179394; ENSMUSP00000136011; ENSMUSG00000060579
GeneIDi14198
KEGGimmu:14198
UCSCiuc007sfj.1 mouse

Organism-specific databases

CTDi2272
MGIiMGI:1277947 Fhit

Phylogenomic databases

eggNOGiKOG3379 Eukaryota
COG0537 LUCA
GeneTreeiENSGT00510000047967
HOGENOMiHOG000164170
HOVERGENiHBG051614
InParanoidiO89106
KOiK01522
PhylomeDBiO89106

Miscellaneous databases

PROiPR:O89106
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000060579 Expressed in 183 organ(s), highest expression level in membranous labyrinth
CleanExiMM_FHIT
ExpressionAtlasiO89106 baseline and differential
GenevisibleiO89106 MM

Family and domain databases

CDDicd01275 FHIT, 1 hit
Gene3Di3.30.428.10, 1 hit
InterProiView protein in InterPro
IPR039383 FHIT
IPR019808 Histidine_triad_CS
IPR001310 Histidine_triad_HIT
IPR011146 HIT-like
IPR036265 HIT-like_sf
PANTHERiPTHR23089 PTHR23089, 1 hit
PfamiView protein in Pfam
PF01230 HIT, 1 hit
SUPFAMiSSF54197 SSF54197, 1 hit
PROSITEiView protein in PROSITE
PS00892 HIT_1, 1 hit
PS51084 HIT_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFHIT_MOUSE
AccessioniPrimary (citable) accession number: O89106
Secondary accession number(s): Q6URW5, Q91VL1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 129 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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